bTMB assays determine TMB using a noninvasive blood test. B-F1RST (ITT, n = 152) is the first prospective trial to evaluate bTMB as a biomarker to predict benefit of 1L atezo monotherapy in advanced NSCLC. bTMB high (score of ≥ 16; ≥ 14.5 mut/Mb) predicted better ORR with atezo vs bTMB low (< 16; 28.6% vs 4.4%) in the biomarker evaluable population (BEP) with ≥ 6 mo follow up in the primary analysis. Numerical benefit for bTMB high was seen in median (m)PFS and mOS. Here we report the B-F1RST final analysis.
Eligibility criteria included untreated stage IIIB-IVB NSCLC and ECOG PS 0/1. Pts received atezo 1200 mg IV q3w until PD, intolerance or loss of benefit. Co-primary endpoints were investigator assessed ORR for efficacy (ITT) and PFS for biomarker analysis (BEP) at a prespecified bTMB cutoff of 16 for high (≥ 16) vs low (< 16). PFS and OS, a secondary endpoint, were further evaluated at various bTMB cutoffs. Serum C-reactive protein (CRP), an inflammation marker in cancer, was evaluated as a surrogate biomarker, ratio of CRP at C3D1 to CRP at screening, to predict PFS and OS.
With ≥ 18 mo follow up (data cutoff, 14 May 2019) in ITT pts, ORR was 17% (95% CI: 12, 24), mPFS was 4.1 mo (95% CI: 2.8, 4.9) and mOS was 14.8 mo (95% CI: 12.7, 21.3). In bTMB ≥ 16 vs < 16, mPFS was 5.0 vs 3.5 mo and mOS was 23.9 vs 13.4 mo (Table). For CRP ratio < 0.5 vs ≥ 0.5, mPFS was 14.1 vs 4.6 mo (HR, 0.43 [90% CI: 0.24, 0.77]), and mOS was NE vs 15.9 mo (HR, 0.30 [90% CI: 0.13, 0.72]). 14% of pts had treatment-related (TR) serious AEs, and 20% had Gr 3-4 TRAEs. 18% of pts had AEs that led to discontinuation. LBA83PFS results Median (95% CI), mo ITT (N = 152) 4.1 (2.8, 4.9) BEP (n = 119) bTMB High (≥ bTMB cutoff) bTMB Low (< bTMB cutoff) HR 90% CI bTMB cutoff Median, mo (n) Median, mo (n) 12 2.6 (44) 4.1 (75) 1.16 0.83, 1.64 16 5.0 (28) 3.5 (91) 0.80 0.54, 1.18 20 6.9 (19) 2.9 (100) 0.59 0.37, 0.93 OS results Median (95% CI), mo ITT (N = 152) 14.8 (12.7, 21.3) BEP (n = 119) bTMB High (≥ bTMB cutoff) bTMB Low (< bTMB cutoff) HR 90% CI bTMB cutoff Median, mo (n) Median, mo (n) 12 15.7 (44) 13.8 (75) 0.95 0.62, 1.46 16 23.9 (28) 13.4 (91) 0.66 0.40, 1.10 20 23.9 (19) 13.1(100) 0.44 0.23, 0.85
B-F1RST shows the clinical utility of bTMB as a predictive biomarker for pts receiving 1L atezo monotherapy. The final analysis confirmed that pts with bTMB ≥ 16 had numerical benefit for PFS and OS. Decrease in serum CRP over 6 wk predicted PFS and OS benefit. No new safety signals were seen.
NCT02848651.
Medical writing assistance was provided by Chris Lum, PhD, of Health Interactions, and funded by F. Hoffmann-La Roche, Ltd.
F. Hoffmann-La Roche, Ltd.
F. Hoffmann-La Roche, Ltd.
M. Socinski: Research grant / Funding (institution), Non-remunerated activity/ies: F. Hoffmann-La Roche. V. Velcheti: Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech, Inc.; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Foundation Medicine. T. Mekhail: Speaker Bureau / Expert testimony: Roche/Genentech. Y.K. Chae: Advisory / Consultancy: Foundation Medicine; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: Biodesix; Honoraria (self): F. Hoffmann La Roche; Honoraria (self): AstraZeneca; Honoraria (self): Merck; Research grant / Funding (institution): BMS. T.A. Leal: Advisory / Consultancy: Genentech, Inc.; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: Bayer; Travel / Accommodation / Expenses, Non-remunerated activity/ies: Mirati Therapeutics. J.E. Dowell: Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Trizell. V. Shen: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/Genentech. S. Hu: Full / Part-time employment: Genentech, Inc.. S.M. Paul: Full / Part-time employment: Genentech, Inc.. D.S. Shames: Full / Part-time employment: Genentech, Inc.. E. Schleifman: Full / Part-time employment: Genentech, Inc.. D.A. Fabrizio: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine, Inc. M. Nowicki: Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann-La Roche. C. Yun: Full / Part-time employment: Genentech, Inc.. S. Phan: Full / Part-time employment: Genentech, Inc.. E.S. Kim: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Takeda. All other authors have declared no conflicts of interest.